Methylazoxymethanol (MAM)-induced brain lesion and oral dyskinesia in rats.
The effects of methylazoxymethanol (MAM)-induced brain lesions on vacuous chewing movements (VCM) were examined in rats given chronic haloperidol treatment (0.1 or 1 mg/kg/day) for 18 months. At the end of the experiment striatal, pallidal, and nigral activities of glutamate decarboxylase (GAD) were measured. MAM-lesioned rats had an elevated rate of VCMs compared to unlesioned controls. This effect was stable during the whole 18-month experiment. In unlesioned control rats chronic haloperidol produced a gradual increase in VCM rates, but this effect was not further exacerbated in MAM-lesioned animals. After chronic haloperidol treatment with the higher dose (1 mg/kg/day) GAD activity was reduced in substantia nigra (-20%), globus pallidus (-35%), and striatum (-26%) of unlesioned rats. MAM caused a reduction of GAD activity in substantia nigra (-29%) and globus pallidus (-29%). Chronic haloperidol did not influence these effects of MAM-induced lesion. The present results show that a MAM-induced brain lesion, in contrast to cortical ablations, cannot be used to amplify the haloperidol-induced VCM increase or influence the nigral GAD activity in a rat model for tardive dyskinesia.
Johansson
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Psychiatric Research Center, University of Uppsala, Sweden.
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced* / Q000503:physiopathology; D003342:Corpus Striatum / Q000502:physiology; D004409:Dyskinesia, Drug-Induced / Q000523:psychology*; D005260:Female; D005917:Globus Pallidus / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006220:Haloperidol / Q000031:analogs & derivatives / Q000494:pharmacology; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D013378:Substantia Nigra / Q000502:physiology
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate; C033563:haloperidol decanoate; D005968:Glutamate Decarboxylase; D006220:Haloperidol; C030667:methylazoxymethanol